1. Field
Embodiments of the present invention relate to a centrifugal micro-fluidic structure for measuring glycated hemoglobin, a centrifugal micro-fluidic device for measuring glycated hemoglobin, and a method for measuring glycated hemoglobin. More particularly, embodiments relate to a micro-fluidic structure wherein only one device simultaneously conducts immunosorbent assay and affinity chromatography measurements, which are particularly selected from various methods for determining glycated hemoglobin, so as to detect hemoglobin variants or interfering substances. The detected results are applied to analysis of measurement results in order to eliminate and/or compensate for, or calibrate errors in measurement of, glycated hemoglobin, thereby more accurately determining the glycated hemoglobin. A centrifugal micro-fluidic device for measuring glycated hemoglobin which includes the foregoing structure, and a method for measuring glycated hemoglobin using the same are also disclosed.
2. Description of the Related Art
In order to flow and move a fluid in a micro-fluidic structure, a driving pressure is generally required. As such a driving pressure, capillary pressure or pressure generated using an additional pump may be used. In recent years, clinical diagnostic analyzers designed to enable a detection of a target material present in a small amount of fluid in simple and economical ways including, for example, a centrifugal micro-fluidic device having a micro-fluidic structure mounted on a circular disk type rotational platform such as lab-on-a disk and/or a lab CD have been proposed.
Lab-on-a disk meaning ‘laboratory on a disk’ is a CD type device in which various components are integrated for analysis of biomolecules used in a laboratory. Upon introducing a biological sample such as blood to the micro-fluidic structure of the disk, a fluid such as a sample, a chemical reagent, etc. may be transferred to a desired location simply by applying centrifugal force without additional driving systems such as driving pressure in order to transport the fluid.
Glycated hemoglobin, or glycosylated hemoglobin, or hemoglobin A1c (hereinafter, sometimes referred to as ‘HbA1c’) has been recognized to be a useful tool for screening for diabetes, checking blood sugar control in people who might be pre-diabetic, or monitoring blood sugar control in patients with diagnosing diabetes mellitus. In the normal 120-day lifespan of the red blood cell, glucose molecules react with hemoglobin, forming glycated hemoglobin. Once a hemoglobin molecule is glycated, it remains that way. A buildup of glycated hemoglobin within the red cell, therefore, reflects the average level of glucose to which the cell has been exposed during its life-cycle. Measuring glycated hemoglobin may assess the effectiveness of therapy of diabetes by monitoring long-term serum glucose regulation. The HbA1c level is proportional to average blood glucose concentration over the previous four weeks to three months.
It has been reported that glycation of hemoglobin has been associated with cardiovascular disease, nephropathy, and retinopathy in diabetes mellitus. Monitoring the HbA1c in type-1 diabetic patients may improve treatment.
When an emergency outpatient testing is required for HbA1c level, the testing should be performed, from starting the test to reporting a result of the test, within 30 minutes and, according to results thereof, further courses of action are determined. Therefore, a rapid and accurate test is required.
At present, a number of test instruments for measuring glycated hemoglobin are commercially available and widely used in the art. These conventional methods for measuring glycated hemoglobin, employ either boronate affinity measurement or immuno-agglutination assay based measurement. The boronate affinity measurement method uses an isolation of glycated hemoglobin from unglycated hemoglobin by a mechanism wherein boronic acid binds to cis-diol of saccharide. The immuno-agglutination assay-based measurement method uses agglutination of an antigen-antibody complex using an antibody specific for the glycated hemoglobin.
However, the foregoing methods have a common drawback of inevitable errors caused by inherent characteristics of each of the methods. For example, in the boronate affinity measurement method, the boronate may be cross-linked with other components receiving cis-diol groups present in blood, thus causing a false decrease in the measured glycated hemoglobin value. On the other hand, the immuno-agglutination method cannot detect hemoglobin variants such as HbF, HbS, HbC, etc., which in turn may cause a false decrease in the measured glycated hemoglobin value.
Consequently, depending on the kinds of hemoglobin variants and/or the measurement methods employed, HbA1c measurement results do not always accurately match clinical status related thereto. Therefore, although both of the foregoing measurement methods must be employed together in order to more precisely determine HbA1c, these methods entail technical difficulties in embodying both of them in a single device since the methods are based on different measurement principles.
Accordingly, there is still a requirement for developing a novel measurement method to overcome the above cited technical restrictions.